1. ¹Dipartimento di Farmacologia Sperimentale via Domenico Montesano 49, Napoli, Italy
2. ²Sezione di Medicina Interna e Scienze Oncologiche, Dipartimento di Medicina Clinica e Sperimentale, Universita' degli Studi di Perugia, Perugia, Italy
3. ³Sezione di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale, Universita' degli Studi di Perugia, Perugia, Italy
4. ⁴Biogen 14, Cambridge Center, Cambridge, Massachusetts

Correspondence: Dr. Giuseppe Cirino, Dipartimento di Farmacologia Sperimentale via Domenico Montesano 49, 80131 Napoli, Italy. Fax: 39 081 7486403; E-mail: cirino@unina.it

Received 5 October 1999.

Abstract

Rats injected in the hind paw with a mixture of Mycobacterium butirricum emulsified in mineral oil (FA) developed a severe polyarthritis that shared some immunological features with human rheumatoid arthritis. After this local administration, rats developed a secondary lesion (edema) in the contralateral paw, which is a hallmark of immune system activation. In vivo intravenous treatment with a monoclonal anti-very late antigen (VLA)-1 antibody (HA31/8) significantly reduced the edema formation in the contralateral paw. T cells isolated from contralateral paw draining lymph nodes of FA rats treated with HA31/8 showed a reduced cell proliferation in vitro, after stimulation with concanavalin A. Furthermore FACS analysis showed that the reduction in proliferation was concomitant to a reduction in the number of T cells positive to surface IL-2 receptor expression. Our data indicate that after in vivo treatment with a monoclonal anti-very late antigen-1 antibody, there is a beneficial effect on the development of the secondary lesion, which correlates to the reduced ability of T cells to proliferate in vitro as well as to a reduced surface expression of IL-2 receptor. The association of this antibody to other drugs interfering at other levels in rheumatoid arthritis may open a new therapeutic window.